JP7601462B2 - Method for preparing levoterbutaline using chiral auxiliary - Google Patents

Description

The present invention belongs to the pharmaceutical technology field, and specifically relates to a method for the chiral preparation of L-terbutaline.

Terbutaline is a fast-acting, short-acting adrenal receptor agonist that can selectively activate β2 receptors, relax bronchial smooth muscles, inhibit the release of endogenous spasmodic substances, and suppress endogenous transmitters and mucociliary activation, thereby relieving edema caused by activation (Non-Patent Document 1: Kyeon H.K., Hyun J.K., Seon-Pyo H., Sang D.S., Arch. Pharm. Res. 2000, 23:441-445). Clinically, it is mainly used to treat bronchial spasms in bronchial asthma, asthmatic bronchitis, emphysema, and chronic obstructive pulmonary disease. Terbutaline has a chiral center of a secondary alcohol, but all of the compounds currently used in clinical practice are racemic. According to research, the levo form of terbutaline is the active ingredient that exerts its medicinal effects (Non-Patent Document 2: J. Med. Chem., 1972, 15, 1182-1183), and the dextro form is not only ineffective but also has toxic side effects. Therefore, researching methods for preparing L-terbutaline and re-marketing this levo form has important clinical value. For example, CN110156614 discloses that when comparing levo(-)terbutaline with the commercially available racemate, the anti-asthma efficacy is doubled, providing a new and preferable treatment method for asthma-related diseases.

The disclosed methods for preparing L-terbutaline are mainly as follows: 1. Decomposition method. Using tartaric acid or tartaric acid derivatives to decompose racemized terbutaline is the simplest and most intuitive method for preparing L-terbutaline (Patent Documents 1-2: CN1273966A, CN201810147612.1). However, such methods often require multiple crystallizations to obtain satisfactory enantiomeric purity, the overall process is complicated, the yield is low, and at least half of the product is discarded, which does not comply with the currently advocated principle of environmentally friendly chemistry.

2. Enzymatic method. The enzymatic reduction method is a common method for preparing chiral secondary alcohols from prochiral ketones, but it requires the selection of an optimal enzyme catalyst and often has drawbacks such as low reduction efficiency (Non-Patent Document 3: Journal of Molecular Catalysis B: Enzymatic, 84, (2012), 83-88).

3. The reduction of prochiral ketones using borane in the presence of a chiral catalyst (Corey-Bakshi-Shibata catalyst or similar) has drawbacks, such as the toxicity of borane and the difficulty of post-treatment, making it difficult to realize industrialized production.

4. The asymmetric reduction of chloroacetophenone is realized by the chiral ruthenium catalyzed transfer hydrogenation method to obtain a key intermediate for the synthesis of L-terbutaline (Non-Patent Document 4: Chem. Pharm. Bull. 65, (2017), 389-395). This method uses expensive precious metals, and the ee of the product is only 91%, which cannot meet the requirements.

Because conventional technology has various deficiencies, it is of great significance to research and develop a new method for preparing L-terbutaline that is simple to operate, highly efficient, and low-cost.

China 1273966A China 201810147612

Kyeong H. K. , Hyun J. K. , Seon-Pyo H. , Sang D. S. , Arch. Pharm. Res. 2000, 23:441-445 J. Med. Chem. , 1972, 15, 1182-1183 Journal of Molecular Catalysis B: Enzymatic, 84, (2012), 83-88 Chem. Pharm. Bull. 65, (2017), 389-395

The object of the present invention is to provide a method for preparing L-terbutaline; the method is simple and reliable, has low preparation cost, and the ee of the chiral product reaches 99.9%.

The technical solution of the present invention is as follows: A method for preparing L-terbutaline using an asymmetric auxiliary, which comprises hydrogenolyzing compound 7 with an alcohol solvent in the presence of a palladium catalyst and hydrochloric acid to obtain L-terbutaline; where the chemical structure of compound 7 is as follows:

Ｌ－テルブタリンの化学構造式は以下のとおりである：

The chemical structure of L-terbutaline is as follows:

In the above technical solution, the palladium catalyst is a palladium carbon catalyst; the alcohol solvent is a low molecular weight alcohol, preferably methanol. Specifically, compound 7 is dissolved in methanol, palladium carbon catalyst is added, hydrochloric acid is added dropwise, hydrogenolysis is carried out with hydrogen at normal pressure for 1 to 3 hours, palladium carbon is removed by filtration, the filtrate is distilled under reduced pressure, and the remaining solid is crystallized to obtain the product L-terbutaline hydrochloride 8.

In the present invention, S-(-)-tert-butylsulfinamide is used as the raw material, which is reacted with 2-bromo-2-methylpropane and 3,5-dibenzyloxybromoacetophenone in sequence to obtain compound 5; compound 5 is reduced under a quaternary ammonium salt catalyst to obtain compound 6; compound 6 is protected by removing tert-butylsulfinyl to obtain intermediate 7. The specific steps and the structural formula of the compound are as follows: (1) Prepare tert-butylsulfinamide-substituted acetophenone intermediate (compound 5). tert-Butylsulfinamide 1
is dissolved in an organic solvent, an alkali is added, then 2-bromo-2-methylpropane is dropped, and the mixture is reacted at 0-60°C for 2-5 hours, and then 3,5-dibenzyloxybromoacetophenone 4 is added, and the mixture is reacted at 30-80°C for 2-8 hours; after the reaction is completed, the mixture is filtered to remove solid substances, and then distilled under reduced pressure to remove the solvent, to obtain compound 5, which is directly used in the next reaction; the organic solvent is acetonitrile, THF, DMF, acetone, toluene or ethyl acetate, preferably acetonitrile, THF and DMF, and more preferably acetonitrile; the alkali is potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, potassium phosphate, potassium fluoride, sodium hydride or potassium tert-butoxide, preferably potassium carbonate and sodium carbonate, and more preferably potassium carbonate; the reaction is as follows:

（２）キラルｔｅｒｔ－ブチルスルフィンアミドの制御かでケトンはキラルアルコール（化合物６）に還元される。化合物５を溶剤に溶解させ、第四級アンモニウム塩を加え、その後０～１０℃で１～２時間以内に数回に分けて水素化ホウ素ナトリウムを加え、完了したら引き続き１時間撹拌し、さらに塩化アンモニウム水溶液を加えてクエンチし、抽出し、乾燥させ、減圧蒸留し、残りの固体にエタノールを用いて結晶化させ、化合物６を得る；前記有機溶剤はＴＨＦ、エタノール、メタノール、イソプロパノールの一種または複数であり、好ましくはＴＨＦおよびイソプロパノールの混合溶剤である；前記の第四級アンモニウム塩はテトラブチルアンモニウムブロミド、テトラブチル塩化アンモニウム、テトラプロピルアンモニウムブロミド、テトラプロピルアンモニウムブロミドまたはトリエチルベンジルアンモニウムブロミドであり、好ましくはテトラブチルアンモニウムブロミドおよびテトラブチル塩化アンモニウムであり、より好ましくはテトラブチルアンモニウムブロミド；反応は以下に示すとおりである。

(2) The ketone is reduced to a chiral alcohol (compound 6) under the control of chiral tert-butylsulfinamide. Compound 5 is dissolved in a solvent, a quaternary ammonium salt is added, and then sodium borohydride is added in several portions within 1-2 hours at 0-10°C. After completion, the mixture is stirred for 1 hour, and then an aqueous ammonium chloride solution is added to quench the mixture, extracted, dried, distilled under reduced pressure, and the remaining solid is crystallized with ethanol to obtain compound 6; the organic solvent is one or more of THF, ethanol, methanol, and isopropanol, and preferably a mixed solvent of THF and isopropanol; the quaternary ammonium salt is tetrabutylammonium bromide, tetrabutylammonium chloride, tetrapropylammonium bromide, tetrapropylammonium bromide, or triethylbenzylammonium bromide, and preferably tetrabutylammonium bromide and tetrabutylammonium chloride, and more preferably tetrabutylammonium bromide; the reaction is as follows:

(3) The tert-butylsulfinyl protection is removed to obtain an intermediate (compound 7). Compound 6 is dissolved in methanol, concentrated hydrochloric acid is added, and the reaction is carried out at 0-60°C for 2-5 hours. The solvent is removed by distillation under reduced pressure, and a saturated solution of sodium bicarbonate is added to the residue, which is extracted with an organic solvent, dried, and distilled under reduced pressure to obtain compound 7, which is used directly in the next reaction. The reaction is as shown below.

(4) The benzyl protection is removed to obtain the target product L-terbutaline. Compound 7 is dissolved in methanol, a palladium carbon catalyst is added, hydrochloric acid is added dropwise, and hydrogenolysis is carried out at normal pressure hydrogen for 1 to 3 hours. The palladium carbon is removed by filtration, and the filtrate is distilled under reduced pressure. The remaining solid is crystallized to obtain R-terbutaline hydrochloride 8. The reaction is as shown below.

To implement the above technical solution, the present invention has the following advantages over the prior art: the present invention uses the first commercialized and inexpensive chiral source tert-butylsulfinamide as the prosthetic group to control the asymmetric reduction of ketones, and the small amount of non-enantiomers can be easily removed by crystallization, with the ee of the product reaching 99.9%; the operation of the entire process is very simple, and all the reagents used are inexpensive, readily available, non-toxic, and very suitable for industrial production.

FIG. 1 is a nuclear magnetic hydrogen spectrum of the hydrochloride salt of R-terbutaline prepared in Example 1. FIG. 2 is a nuclear magnetic carbon spectrum of the hydrochloride salt of R-terbutaline prepared in Example 1. FIG. 3 is a mass spectrum of the hydrochloride salt of R-terbutaline prepared in Example 1. FIG. 4 is a liquid chromatogram of the hydrochloride salt of R-terbutaline prepared in Example 1. FIG. 5 is a liquid chromatogram of conventional racemic terbutaline (Hiromori Pharmaceutical Co., Ltd.).

The specific preparation and testing methods of the present invention are general methods, for example, the purity and ee value are tested by general liquid chromatography (HPLC + chiral column). The present invention will be described in more detail below in combination with examples.

The preparation method of the present invention is as follows:

Example 1.

S-(-)-tert-butylsulfinamide 1 (14.8 g, 110 mmol) was dissolved in acetonitrile (300 mL), potassium carbonate (18.0 g, 130 mmol) was added, then 2-bromo-2-methylpropane (17.8 g, 130 mmol) was added dropwise, and the mixture was heated to 50°C for 4 hours, after which 3,5-dibenzyloxybromoacetophenone 4 (41.1 g, 100 mmol) was added, and the mixture was heated to 60°C for 6 hours. After the reaction was completed, the solid material was removed by filtration, and then the solvent was removed by vacuum distillation to obtain compound 5, which was directly used in the next reaction.

The compound 5 obtained above was dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) was added, the reaction system was cooled to 0°C, and then sodium borohydride (3.02 g, 80 mmol) was uniformly added in three portions within 1.5 hours. After the conversion was completed, the mixture was stirred at 0°C for 1 hour, quenched by adding aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts were combined, sodium sulfate was dried, and the mixture was distilled under reduced pressure. The remaining solid was crystallized from ethanol (90 mL) to obtain 37.1 g of white solid compound 6, with a two-stage yield of 71%.

Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added, and the mixture was allowed to react at 50°C for 3 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was added with saturated sodium bicarbonate solution (80 mL), extracted three times with ethyl acetate, the organic layers were combined, the sodium sulfate was dried, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was used directly in the next reaction.

The compound 7 obtained above was dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) was added, 2 mol/L hydrogen chloride methanol solution (25 mL) was added dropwise, and then hydrogenolysis was performed under normal pressure hydrogen for 2 hours, followed by filtration to remove palladium carbon, and the filtrate was subjected to general reduced pressure distillation to remove the solvent, and the remaining solid was crystallized from tetrahydrofuran (100 mL), obtaining a total of 11.7 g of R-terbutaline hydrochloride 8, with a two-step yield of 85%, a purity of 99.7%, an ee of 99.9%, and an optical rotation [a] D20 = -39.2 (c = 1.0 in MeOH).

Example 2.

Based on Example 1, potassium carbonate (18.0 g, 130 mmol) was replaced with sodium carbonate (130 mmol), and the rest was left unchanged to obtain R-terbutaline hydrochloride 8 with a purity of 99.6% and an ee of 99.7%.

Based on Example 1, tetrabutylammonium bromide (3.22 g, 10 mmol) was replaced with tetrabutylammonium chloride (10 mmol), and the rest was left unchanged to obtain R-terbutaline hydrochloride 8 with a purity of 99.5% and an ee of 99.1%.

Based on Example 1, but changing isopropanol (200 mL) to ethanol (200 mL) and leaving the rest unchanged, R-terbutaline hydrochloride 8 was obtained with a purity of 99.1% and an ee of 99.2%.

Comparative Example 1.

Based on Example 1, omitting tetrabutylammonium bromide and leaving the rest unchanged, the two-step yield of compound 6 is 55%, and further R-terbutaline hydrochloride 8 is obtained, with an ee of 95.2%.

Based on Example 1, the mixed solvent of THF (200 mL) and isopropanol (200 mL) was changed to isopropanol (400 mL), and the rest was left unchanged. The two-step yield of compound 6 was 60%, and further R-terbutaline hydrochloride 8 was prepared, with an ee of 98.8%.

Based on Example 1, sodium borohydride (3.02 g, 80 mmol) was changed to potassium borohydride (80 mmol) and the rest was left unchanged, the two-step yield of compound 6 was 59%, and further R-terbutaline hydrochloride 8 was prepared with an ee of 98.3%.

Example 3.

S-(-)-tert-butylsulfinamide 1 (14.8 g, 110 mmol) is dissolved in acetonitrile (300 mL), potassium carbonate (18.0 g, 130 mmol) is added, then 2-bromo-2-methylpropane (17.8 g, 130 mmol) is added dropwise, and the mixture is heated to 40°C and reacted for 3 hours, after which 3,5-dibenzyloxybromoacetophenone 4 (41.1 g, 100 mmol) is added, and the mixture is reacted at 60°C for 6 hours. After the reaction is complete, the solid material is removed by filtration, and then the solvent is removed by vacuum distillation to obtain compound 5, which is directly used in the next reaction.

The compound 5 obtained above is dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) is added, the reaction system is cooled to 0°C, and then sodium borohydride (3.02 g, 80 mmol) is uniformly added in three portions within 1.5 hours. After the addition is completed, the mixture is stirred at 0°C for 1 hour, quenched by adding aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts are combined, sodium sulfate is dried, and the mixture is distilled under reduced pressure. The remaining solid is crystallized from ethanol (90 mL) to obtain a white solid compound 6.

Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added, and the mixture was reacted at 50°C for 3 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was added with saturated sodium bicarbonate solution (80 mL), extracted three times with ethyl acetate, the organic layers were combined, the sodium sulfate was dried, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was directly used in the next reaction.

The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, 2 mol/L hydrogen chloride methanol solution (25 mL) is added dropwise, and then hydrogenolysis is performed under normal pressure hydrogen for 2 hours, followed by filtration to remove the palladium carbon, and the filtrate is subjected to general reduced pressure distillation to remove the solvent, and the remaining solid is crystallized from tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

Example 4.

S-(-)-tert-butylsulfinamide 1 (14.8 g, 110 mmol) was dissolved in acetonitrile (300 mL), potassium carbonate (18.0 g, 130 mmol) was added, then 2-bromo-2-methylpropane (17.8 g, 130 mmol) was added dropwise, and the mixture was heated to 50°C for 4 hours, after which 3,5-dibenzyloxybromoacetophenone 4 (41.1 g, 100 mmol) was added, and the mixture was heated to 60°C for 6 hours. After the reaction was completed, the solid material was removed by filtration, and then the solvent was removed by vacuum distillation to obtain compound 5, which was directly used in the next reaction.

The obtained compound 5 is dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) is added, the reaction system is cooled to 5°C, and then sodium borohydride (3.02 g, 80 mmol) is uniformly added in two portions within 1 hour. After the addition is completed, the mixture is stirred at 0°C for 1 hour, quenched by adding aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts are combined, sodium sulfate is dried, and the mixture is distilled under reduced pressure. The remaining solid is crystallized from ethanol (90 mL) to obtain a white solid compound 6.

Compound 6 (26.1 g, 50 mmol) is dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) is added, and the mixture is reacted at 50°C for 3 hours. After the reaction is completed, the solvent is removed by distillation under reduced pressure, a saturated solution of sodium bicarbonate (80 mL) is added to the residue, and the mixture is extracted three times with ethyl acetate. The organic layers are combined, the sodium sulfate is dried, and the solvent is removed by distillation under reduced pressure to obtain compound 7, which is used directly in the next reaction.

The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, 2 mol/L hydrogen chloride methanol solution (25 mL) is added dropwise, and then hydrogenolysis is performed with hydrogen at normal pressure for 2.5 hours, followed by filtration to remove the palladium carbon, and the filtrate is subjected to general reduced pressure distillation to remove the solvent. The remaining solid is crystallized in tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

Example 5.

S-(-)-tert-butylsulfinamide 1 (14.8 g, 110 mmol) was dissolved in acetonitrile (300 mL), potassium carbonate (18.0 g, 130 mmol) was added, then 2-bromo-2-methylpropane (17.8 g, 130 mmol) was added dropwise, and the mixture was heated to 50°C for 4 hours, after which 3,5-dibenzyloxybromoacetophenone 4 (41.1 g, 100 mmol) was added, and the mixture was heated to 60°C for 6 hours. After the reaction was completed, the solid material was removed by filtration, and then the solvent was removed by vacuum distillation to obtain compound 5, which was directly used in the next reaction.

The obtained compound 5 is dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) is added, the reaction system is cooled to 0°C, and then sodium borohydride (3.02 g, 80 mmol) is uniformly added in three portions within 1.5 hours. After the conversion is completed, the mixture is stirred at 0°C for 1 hour, quenched by adding aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts are combined, the sodium sulfate is dried, and the mixture is distilled under reduced pressure. The remaining solid is crystallized from ethanol (90 mL) to obtain a white solid compound 6.

Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added, and the mixture was reacted at 50°C for 4 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was added with saturated sodium bicarbonate solution (80 mL), extracted three times with ethyl acetate, the organic layers were combined, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was directly used in the next reaction.

The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, and the mixture is hydrogenolyzed with 2 mol/L hydrogen chloride methanol solution (25 mL) and then at atmospheric pressure for 2 hours. The mixture is then filtered to remove the palladium carbon, and the filtrate is subjected to a general vacuum distillation to remove the solvent. The remaining solid is crystallized in tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

Example 6.

S-(-)-tert-butylsulfinamide 1 (14.8 g, 110 mmol) is dissolved in acetonitrile (300 mL), potassium carbonate (18.0 g, 130 mmol) is added, then 2-bromo-2-methylpropane (17.8 g, 130 mmol) is added dropwise, and the mixture is heated to 50°C and reacted for 4 hours, after which 3,5-dibenzyloxybromoacetophenone 4 (41.1 g, 100 mmol) is added, and the mixture is reacted at 60°C for 6 hours. After the reaction is complete, the solid material is removed by filtration, and then the solvent is removed by vacuum distillation to obtain compound 5, which is directly used in the next reaction.

The obtained compound 5 is dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) is added, the reaction system is cooled to 0 ° C, and then sodium borohydride (3.02 g, 80 mmol) is uniformly added in three portions within 1.5 hours. After the conversion is completed, the mixture is stirred at 0 ° C for 1 hour, quenched by adding aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts are combined, sodium sulfate is dried, and the mixture is distilled under reduced pressure. The remaining solid is crystallized from ethanol (90 mL) to obtain a white solid compound 6.

Compound 6 (26.1 g, 50 mmol) is dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) is added, and the mixture is reacted at 50°C for 3 hours. After the reaction is completed, the solvent is removed by distillation under reduced pressure, a saturated solution of sodium bicarbonate (80 mL) is added to the residue, and the mixture is extracted three times with ethyl acetate. The organic layers are combined, the sodium sulfate is dried, and the solvent is removed by distillation under reduced pressure to obtain compound 7, which is used directly in the next reaction.

The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, 2 mol/L hydrogen chloride methanol solution (25 mL) is added dropwise, and then hydrogenolysis is performed with hydrogen at normal pressure for 2.5 hours, followed by filtration to remove the palladium carbon, and the filtrate is subjected to general reduced pressure distillation to remove the solvent. The remaining solid is crystallized in tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

The method provided by the present invention uses inexpensive and readily available chiral tert-butylsulfinamide as an asymmetric auxiliary to control the chiral secondary alcohol required for asymmetric reduction of ketones, and the asymmetric auxiliary can be removed under simple acidic conditions.

Claims (10)

Compound 7:

And
Compound 7 is hydrogenolyzed in an alcohol solvent in the presence of a palladium catalyst and hydrochloric acid ;
L-Terbutaline as follows:

1. A method for preparing L-terbutaline using a chiral auxiliary, comprising obtaining Using S- (−) -tert-butylsulfinamide as a chiral auxiliary as a raw material , the compound was reacted with 2-bromo-2-methylpropane and 3,5-dibenzyloxybromoacetophenone in this order to obtain the following compound 5:

And
Compound 5 is hydrogenated in the presence of a quaternary ammonium salt and reduced to give compound 6:

And
A method for preparing L-terbutaline using the chiral auxiliary of claim 1, which comprises removing the tert -butylsulfinyl protection of compound 6 to give compound 7. The method for producing L-terbutaline using the chiral auxiliary according to claim 2, comprising dissolving tert-butylsulfinamide in an organic solvent, adding an alkali, then dropping 2-bromo-2-methylpropane, reacting at 0 to 60°C for 2 to 5 hours, then adding 3,5-dibenzyloxybromoacetophenone, and continuing to react at 30 to 80°C for 2 to 8 hours to obtain compound 5. A method for preparing L-terbutaline using the chiral auxiliary according to claim 2, comprising dissolving compound 5 in a solvent, adding a quaternary ammonium salt, and then adding sodium borohydride at 0 to 10°C to carry out a reduction reaction to obtain compound 6. A method for preparing L-terbutaline using the chiral auxiliary according to claim 2, comprising dissolving compound 6 in an alcohol solvent, adding concentrated hydrochloric acid, and reacting at 0 to 60° C. for 2 to 5 hours to obtain compound 7. the palladium catalyst is an inorganic palladium catalyst;
2. The method for preparing L-terbutaline using the chiral auxiliary according to claim 1, wherein the alcohol solvent is methanol . the palladium catalyst is a palladium on carbon catalyst;
The method for preparing L-terbutaline using the chiral auxiliary according to claim 6, wherein the alcohol solvent is methanol. The method for preparing L-terbutaline using the chiral auxiliary according to claim 1, comprising dissolving compound 7 in an alcohol solvent, adding a palladium catalyst, adding hydrochloric acid dropwise, and hydrogenolysis under normal pressure of hydrogen for 1 to 3 hours to obtain the product L-terbutaline. Use of S-(-)-tert-butylsulfinamide in the preparation of L-terbutaline. The structural formula:

A compound characterized by being used for L-terbutaline having the formula:

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